Endothelial cells are located at the luminal surface of blood vessels and are involved in many important functions and some diseased states. The glycocalyx of the endothelial cell layer provides a surface of low thrombogenic nature. One important component of this layer is the highly negatively charged endothelial heparan sulfate. Both endogenous heparan sulfate and heparin are bound to endothelial cell surfaces in vitro through a receptor which recognizes both molecules. Endothelial heparan sulfate and heparin inhibit vascular smooth muscle cell proliferation and migration. In addition, the excessive matrix build-up that occurs in atherosclerosis is notable for its decreased percent of heparan sulfate. The endothelial receptors for heparan sulfate may interact with extracellular matrix heparan sulfate proteoglycans in addition to the glycocalyx heparan sulfate proteoglycans. This research proposal aims to study the cell activities which respond to the absence or presence of ligands (heparan sulfate proteoglycans or heparin) on the heparan sulfate receptors. These studies will lead to a better understanding of endothelial cell control of heparan sulfate concentrations in the glycocalyx and intimal matrix.